H3K27 acetylation promotes IncRNA OIP5-AS1 transcription and induces apoptosis of nasal epithelial cells in allergic rhinitis through up-regulation of TLR4
Objective To investigate the effect of lysine 27 residue of histone H3(H3K27)acetylation modification on the transcriptional promotion of long noncoding RNA OPA interacting protein 5-antisense RNA 1(IncRNA 0IP5-AS1)and apoptosis of nasal epithelial cells(NECs)in allergic rhinitis(AR)via regulating Toll-like receptor 4(TLR4).Methods Interleukin-13(IL-13)was used to treat NECs to establish an AR cell model.Real-time quantitative PCR was utilized to detect the expressions of OIP5-AS1 and TLR4 in nasal mucosal tissues of AR patients and in the in vitro cell model.The concentrations of macrophage colony-stimulating factor(GM-CSF),eotaxin-1,and mucin 5AC(MUC5AC)were detected by ELISA.The apoptosis of NECs was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL).A dual-luciferase report experiment was carried out to verify the relationship between OIP5-AS1 and TLR4.Chromatin immunoprecipitation(ChIP)assay was performed to verify H3K27 acetylation of histones in the 0IP5-AS1 promoter region.Results Compared with healthy controls and untreated NECs,OIP5-AS1 and TLR4 were both up-regulated in nasal mucosal tissues from AR patients and IL-13-stimulated NECs.Knockdown of OIP5-ASl decreased the level of TLR4 in IL-13-treated NECs,while overexpression of OIP5-AS1 increased the level of TLR4.Inhibition of OIP5-AS1 reduced the apoptosis rate,and inhibited the secretion of GM-CSF,eotaxin-1,and MUC5AC from IL-13-treated NECs,while overexpression of TLR4 partially reversed the effects of OIP5-AS1 knockdown on NEC apoptosis and the secretion of GM-CSF,eotaxin-1,and MUC5AC.In addition,H3K27 acetylation was markedly enriched in the promoter region of OIP5-AS1,and H3K27 acetylation promoted the expression of OIP5-AS1 in IL-13-treated NECs.Conclusion H3K27 acetylation promotes OIP5-AS1 transcription and induces NEC apoptosis in AR via upregulation of TLR4.
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